tbuckley/cabot-search huggingface dataset:
A phase 1b randomized clinical trial of CT1812 to measure Aβ oligomer displacement in Alzheimer’s disease using an indwelling CSF catheter
Authors: Kelsie M LaBarbera, Yvette I Sheline, Nicholas J Izzo, Carla M Yuede, Lora Waybright, Raymond Yurko, Hannah M Edwards, Woodrow D Gardiner, Kaj Blennow, Henrik Zetterberg, Anne Börjesson-Hanson, Roger Morgan, Charles S Davis, Robert J Guttendorf, Lon S Schneider, Steven DeKosky, Harry LeVine, Michael Grundman, Anthony O Caggiano, John R Cirrito, Susan M Catalano, Mary E Hamby
Journal: Translational Neurodegeneration (2023)

NCT03522129 https:// clini caltr ials.gov/ ct2/ show/ NCT03 522129.Investigational therapies for Alzheimer's disease (AD) target a wide range of mechanisms, yet promising disease-modifying therapies remain a huge unmet need.Much evidence indicates that the oligomeric form of amyloid-beta (Aβ) is a toxic species contributing to AD through synaptic damage and neuronal toxicity [1].In support of this, Aβ oligomer reduction in an AD mouse model leads to memory preservation [2, 3], and clinical benefit was observed in trials of lecanemab, which targets Aβ oligomers and protofibrils [4], in AD patients, encouraging the continued development of Aβ oligomertargeting therapies.CT1812 is a novel, small-molecule, brain-penetrant sigma-2 receptor (S2R) modulator that selectively prevents and displaces Aβ oligomers from binding to neuronal synapses, thereby mitigating downstream toxicity.This is thought to occur through allosteric modulation
Efficiency Encapsulation of FK506 with New Dual Self‐Assembly Multi‐Hydrophobic‐Core Nanoparticles for Preventing Keratoplasty Rejection
Authors: Dongmei Wang, Baoshan Huang, Chenchen Zhu, Lei Wang, Jiahui Jin, Jingyang Tan, Qing Li, Shengjin Xiang, Kaihui Nan, Sen Lin
Journal: Advanced Healthcare Materials (2023)

Nanoparticles self-assembled by amphiphilic copolymers for loading hydrophobic molecules are intensively investigated. However, their hydrophobic molecule-loading capacity is low due to the limitation of hydrophobic groups in these copolymers. In this regard, new lysine oligomer-based multi-hydrophobic side chain polymers (MHCPs) are synthesized by polymerization of γ-benzyl-l glutamate N-carboxy anhydride initiated by side-chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs can be self-assembled by hydrophobic interaction to form multi-hydrophobic-core nanoparticles (MHC-NPs) with silkworm cocoon-, grape cluster-, and butterfly-like shapes (depending on hydrophobic-side-chains lengths). To increase their stability, MHC-NPs are dually self-assembled with polyethylene glycol-polyglutamic acid through charge interaction. Each hydrophobic core in MHC-NPs serves as a carrier for hydrophobic molecules, endowing their nanostructure with high loading capacity. MHC-NPs are employed to load tacrolimus (also known as FK506), and the loading amount is 18% and the loading efficiency is 80%, which are higher than those of previously reported nanomicelles self-assembled by linear amphiphilic copolymers. Topical administration of FK506-loaded nanoparticle (FK506-NP) can significantly prolong retention of FK506 on the eye surface. FK506-NP exhibits higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty.
Author correction to “DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis” [Acta Pharmaceutica Sinica B 12 (2022) 262–273]
Authors: Yuanyuan Wang, Bin Wei, Danping Wang, Jingjing Wu, Jianhua Gao, Haiqing Zhong, Yang Sun, Qiang Xu, Wen Liu, Yanhong Gu, Wenjie Guo
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2021.03.043.].
Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8+ T cells in the tumor microenvironment
Authors: Jie Cheng, Jinxin Yan, Ying Liu, Jiangzhou Shi, Haoyu Wang, Hanyang Zhou, Yinglin Zhou, Tongcun Zhang, Lina Zhao, Xianbin Meng, Haipeng Gong, Xinxiang Zhang, Haichuan Zhu, Peng Jiang
Journal: Cell Metabolism (2023)
Novel agents and evolving strategies in myelofibrotive neoplasm: an update from 2022 ASH annual conference
Authors: Andrew Wang, James Liu, Jeffrey J. Pu
Journal: Journal of Hematology & Oncology (2023)

Abstract Myelofibrosis (MF) is a disorder characterized by the proliferation of myeloid precursors, commonly due to overactive JAK signaling. The discovery of the JAK2 V617F mutation and subsequent development of JAK inhibitors (JAKi) results in reduced spleen size, improved symptom, and enhanced survival in MF patients. However, there are unmet needs of additional novel targeted therapies for this incurable disease due to the limited utility of first-generation JAKis, which are associated with dose-limiting cytopenia and disease recurrence. New targeted treatment strategies for MF are on the horizon. We are here to discuss the latest clinical research findings presented in the 2022 ASH Annual Meeting.
Letter concerning “Objective response rate targets for recurrent glioblastoma clinical trials based on the historic association between ORR and median overall survival”: Toward surrogate endpoints for phase II trials in patients with recurrent glioblastoma
Authors: Vincenzo Di Nunno, Lidia Gatto, Alicia Tosoni, Stefania Bartolini, Enrico Franceschi
Journal: Neuro-Oncology (2023)

Journal Article Letter concerning "Objective response rate targets for recurrent glioblastoma clinical trials based on the historic association between ORR and median overall survival": Toward surrogate endpoints for phase II trials in patients with recurrent glioblastoma Get access Vincenzo Di Nunno, Vincenzo Di Nunno Department of Oncology, Azienda Unità Sanitaria Locale (AUSL) Bologna, 40139 Bologna, Italy https://orcid.org/0000-0003-4441-9834 Search for other works by this author on: Oxford Academic PubMed Google Scholar Lidia Gatto, Lidia Gatto Department of Oncology, Azienda Unità Sanitaria Locale (AUSL) Bologna, 40139 Bologna, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Alicia Tosoni, Alicia Tosoni Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Stefania Bartolini, Stefania Bartolini Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy Search for other works by this author on: Oxford Academic PubMed Google Scholar Enrico Franceschi Enrico Franceschi Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy Corresponding Author: Enrico Franceschi, MD, Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy (e.franceschi@isnb.it). https://orcid.org/0000-0001-9332-4677 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, Volume 25, Issue 8, August 2023, Pages 1546–1547, https://doi.org/10.1093/neuonc/noad071 Published: 12 May 2023 Article history Corrected and typeset: 12 May 2023 Published: 12 May 2023
European Association of Urology Guidelines on Testicular Cancer: 2023 Update
Authors: Anna Patrikidou, Walter Cazzaniga, Daniel Berney, Joost Boormans, Isabel de Angst, Domenico Di Nardo, Christian Fankhauser, Stefanie Fischer, Carmen Gravina, Hendrik Gremmels, Axel Heidenreich, Florian Janisch, Ricardo Leão, Nicola Nicolai, Christoph Oing, Jan Oldenburg, Robert Shepherd, Torgrim Tandstad, David Nicol
Journal: European Urology (2023)
Cross-phyla protein annotation by structural prediction and alignment
Authors: Fabian Ruperti, Nikolaos Papadopoulos, Jacob M Musser, Milot Mirdita, Martin Steinegger, Detlev Arendt
Journal: Genome biology (2023)

Abstract Background Protein annotation is a major goal in molecular biology, yet experimentally determined knowledge is typically limited to a few model organisms. In non-model species, the sequence-based prediction of gene orthology can be used to infer protein identity; however, this approach loses predictive power at longer evolutionary distances. Here we propose a workflow for protein annotation using structural similarity, exploiting the fact that similar protein structures often reflect homology and are more conserved than protein sequences. Results We propose a workflow of openly available tools for the functional annotation of proteins via structural similarity ( MorF : Mor pholog F inder) and use it to annotate the complete proteome of a sponge. Sponges are highly relevant for inferring the early history of animals, yet their proteomes remain sparsely annotated. MorF accurately predicts the functions of proteins with known homology in $${&gt;}90\%$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mo>&gt;</mml:mo> <mml:mn>90</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> cases and annotates an additional $$50\%$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>50</mml:mn> <mml:mo>%</mml:mo> </mml:mrow> </mml:math> of the proteome beyond standard sequence-based methods. We uncover new functions for sponge cell types, including extensive FGF, TGF, and Ephrin signaling in sponge epithelia, and redox metabolism and control in myopeptidocytes. Notably, we also annotate genes specific to the enigmatic sponge mesocytes, proposing they function to digest cell walls. Conclusions Our work demonstrates that structural similarity is a powerful approach that complements and extends sequence similarity searches to identify homologous proteins over long evolutionary distances. We anticipate this will be a powerful approach that boosts discovery in numerous -omics datasets, especially for non-model organisms.
Comparison of the 2022 and 2017 European LeukemiaNet risk classifications in a real-life cohort of the PETHEMA group
Authors: Claudia Sargas, Rosa Ayala, María J Larráyoz, María C Chillón, Eduardo Rodriguez-Arboli, Cristina Bilbao, Esther Prados de la Torre, David Martínez-Cuadrón, Rebeca Rodríguez-Veiga, Blanca Boluda, Cristina Gil, Teresa Bernal, Juan Bergua, Lorenzo Algarra, Mar Tormo, Pilar Martínez-Sánchez, Elena Soria, Josefina Serrano, Juan M Alonso-Dominguez, Raimundo García, María Luz Amigo, Pilar Herrera-Puente, María J Sayas, Esperanza Lavilla-Rubira, Joaquín Martínez-López, María J Calasanz, Ramón García-Sanz, José A Pérez-Simón, María T Gómez Casares, Joaquín Sánchez-García, Eva Barragán, Pau Montesinos
Journal: Blood Cancer Journal (2023)

Abstract Next-Generation Sequencing is needed for the accurate genetic risk stratification of acute myeloid leukemia according to European LeukemiaNet (ELN) guidelines. We validated and compared the 2022 ELN risk classification in a real-life cohort of 546 intensively and 379 non-intensively treated patients. Among fit patients, those aged ≥65 years old showed worse OS than younger regardless risk classification. Compared with the 2017 classification, 14.5% of fit patients changed the risk with the 2022 classification, increasing the high-risk group from 44.3% to 51.8%. 3.7% and 0.9% FLT3 -ITD mutated patients were removed from the favorable and adverse 2017 categories respectively to 2022 intermediate risk group. We suggest that midostaurin therapy could be a predictor for 3 years OS (85.2% with vs. 54.8% without midostaurin, P = 0.04). Forty-seven (8.6%) patients from the 2017 intermediate group were assigned to the 2022 adverse-risk group as they harbored myelodysplasia (MDS)-related mutations. Patients with one MDS-related mutation did not reach median OS, while patients with ≥2 mutations had 13.6 months median OS ( P = 0.002). Patients with TP53 ± complex karyotype or inv(3) had a dismal prognosis (7.1 months median OS). We validate the prognostic utility of the 2022 ELN classification in a real-life setting providing supportive evidences to improve risk stratification guidelines.
Targeted therapy for rare lung cancers: Status, challenges, and prospects
Authors: Chunsen Wang, Xiang Yuan, Jianxin Xue
Journal: Molecular Therapy (2023)

Lung cancer causes the most cancer-related deaths worldwide. In recent years, molecular and immunohistochemical techniques have rapidly developed, further inaugurating an era of personalized medicine for lung cancer. The rare subset of lung cancers accounts for approximately 10%, each displaying distinct clinical characteristics. Treatments for rare lung cancers are mainly based on evidence from common counterparts, which may lead to unsolid clinical benefits considering intertumoral heterogeneity. The increasing knowledge of molecular profiling of rare lung cancers has made targeting genetic alterations and immune checkpoints a powerful strategy. Additionally, cellular therapy has emerged as a promising way to target tumor cells. In this review, we first discuss the current status of targeted therapy and preclinical models for rare lung cancers, as well as provide mutational profiles by integrating the results of existing cohorts. Finally, we point out the challenges and future directions for developing targeted agents for rare lung cancer.
Tellurium-driven maple leaf-shaped manganese nanotherapeutics reshape tumor microenvironment via chemical transition in situ to achieve highly efficient radioimmunotherapy of triple negative breast cancer
Authors: Wei Huang, Sujiang Shi, Haoran Lv, Zhenyu Ju, Qinghua Liu, Tianfeng Chen
Journal: Bioactive Materials (2023)

The therapeutic efficacy of radioimmunotherapy against triple negative breast cancer (TNBC) is largely limited by the complicated tumor microenvironment (TME) and its immunosuppressive state. Thus developing a strategy to reshape TME is expected to achieve highly efficient radioimmunotherapy. Therefore, we designed and synthesized a tellurium (Te)-driven maple leaf manganese carbonate nanotherapeutics (MnCO
Blood Contacts During Surgical Procedures
Authors: Adelisa L. Panlilio
Journal: JAMA (1991)

Operating room personnel are at risk for infection with blood-borne pathogens through blood contact. To describe the nature and frequency of blood contact and its risk factors, trained observers monitored a sample of operations performed by six surgical services at Grady Memorial Hospital, Atlanta, Ga, for 6 months. In 62 (30.1%) of 206 operations, at least one blood contact was observed. Of 1828 operating room person-procedures observed, 96 (5.3%) had 147 blood contacts (133 skin contacts [90%], 10 percutaneous injuries [7%], and four eye splashes [3%]). The mean number of blood contacts per 100 personprocedures was highest for surgeons (18.6). The frequency of percutaneous injury was similar among surgeons and scrub staff (mean, 1.2 per 100 workerprocedures for each group). Risk factors for surgeons' blood contacts were (1) performing a trauma, burn, or orthopedic emergency procedure (odds ratio [OR], 4.1; 95% confidence interval [CI], 2.0 to 8.7); (2) patient blood loss exceeding 250mL ([ill] 2.1; 95% CI, 1.2 to 3.7); and (3) being in the operating room longer than 1 hour (OR, 3.3; 95% CI, 1.6 to 7.1). Of 110 blood contacts among surgeons, 81 (74%) were potentially preventable by additional barrier precautions, such as face shields and fluid-resistant gowns. Twenty-one (84%) of 25 blood contacts among surgeons in procedures in which all three risk factors were present were potentially preventable by additional barriers. Of 29 blood contacts among anesthesia and circulating personnel, 20 (69%) would have been prevented by glove use. For surgical procedures in which operating room personnel are at increased risk of blood contact, reevaluation of surgical technique, use of appropriate barrier precautions, and development of punctureresistant glove materials are indicated. (<i>JAMA</i>. 1991;265:1533-1537)
AACVPR/ACC/AHA 2007 Performance Measures on Cardiac Rehabilitation for Referral to and Delivery of Cardiac Rehabilitation/Secondary Prevention Services
Authors: Randal Thomas, Marjorie King, Karen Lui, Neil Oldridge, Ileana Piña, John Spertus, Robert Bonow, N Estes, David Goff, Kathleen Grady, Ann Hiniker, Frederick Masoudi, Martha Radford, John Rumsfeld, Gayle Whitman
Journal: Circulation (2007)

Check each therapy prescribed or check contraindication reason.Aspirin: next dose due (date/time)____________/____________ No aspirin, reason documented in discharge summary.Clopidogrel: next dose due (date/time)____________/____________ No clopidogrel, reason documented in discharge summary.Beta blocker: next dose due (date/time)____________/____________ No beta blocker, reason in discharge summary.ACE inhibitor: next dose due (date/time)____________/____________ No ACE inhibitor, reason documented in discharge summary.Statin or other lipid-lowering agent (LLA): next dose due (date/time)_________/__________ No statin or other LLA, reason documented in discharge summary.Cardiac rehabilitation referral made, patient information communicated to program, and program information/appointment communicated to patient No exercise prescription and/or cardiac rehabilitation referral with reason in discharge summary.Smoking cessation teaching and pharmacological therapy given (patient is a current smoker or former smoker of less than 1 year) or Smoking cessation teaching and pharmacological therapy not required (patient is nonsmoker or former smoker of greater than 1 year).Education on warning signs of MI and what to do if symptoms given.Education not given, reason documented in discharge summary.Diet: low-fat, low-cholesterol, no added salt ______________________________________ Follow-up appointment documented in medical record.
Localized Sources Maintaining Atrial Fibrillation Organized by Prior Ablation
Authors: Michel Haïssaguerre, Mélèze Hocini, Prashanthan Sanders, Yoshihide Takahashi, Martin Rotter, Frederic Sacher, Thomas Rostock, Li-Fern Hsu, Anders Jonsson, Mark D. O’Neill, Pierre Bordachar, Sylvain Reuter, Raymond Roudaut, Jacques Clémenty, Pierre Jaïs
Journal: Circulation (2006)

Background— Endocardial mapping of localized sources driving atrial fibrillation (AF) in humans has not been reported. Methods and Results— Fifty patients with AF organized by prior pulmonary vein and linear ablation were studied. AF was considered organized if mapping during AF showed irregular but discrete atrial complexes exhibiting consistent activation sequences for &gt;75% of the time using a 20-pole catheter with 5 radiating spines covering 3.5-cm diameter or sequential conventional mapping. A site or region centrifugally activating the remaining atrial tissue defined a source. During AF with a cycle length of 211±32 ms, activation mapping identified 1 to 3 sources at the origin of atrial wavefronts in 38 patients (76%) predominantly in the left atrium, including the coronary sinus region. Electrograms at the earliest area varied from discrete centrifugal activation to an activity spanning 75% to 100% of the cycle length in 42% of cases, the latter indicating complex local conduction or a reentrant circuit. A gradient of cycle length (&gt;20 ms) to the surrounding atrium was observed in 28%. Local radiofrequency ablation prolonged AF cycle length by 28±22 ms and either terminated AF or changed activation sequence to another organized rhythm. In 4 patients, the driving source was isolated, surrounded by the atrium in sinus rhythm, and still firing at high frequency (228±31 ms) either permanently or in bursts. Conclusions— AF associated with consistent atrial activation sequences after prior ablation emanates mostly from localized sources that can be mapped and ablated. Some sources harbor electrograms suggesting the presence of localized reentry.
Noninvasive Ventilation in Cardiogenic Pulmonary Edema
Authors: Stefano Nava, Giorgio Carbone, Nicola DiBattista, Andrea Bellone, Paola Baiardi, Roberto Cosentini, Mauro Marenco, Fabrizio Giostra, Guido Borasi, Paolo Groff
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p = 0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients.
Pulmonary Sarcoidosis
Authors: Gary W. Hunninghake, Ronald G. Crystal
Journal: New England Journal of Medicine (1981)

Using the monoclonal antibodies OKT4 and OKT8, we determined the proportions of helper and suppressor T cells in patients with sarcoidosis and high-intensity alveolitis, patients with sarcoidosis and low-intensity alveolitis, patients with idiopathic pulmonary fibrosis (IPF), and normal controls. In controls and patients with IPF, the ratio of helper to suppressor T cells was 1.8:1 in lungs and blood. In contrast, this ratio was 10.5:1 in lungs (P<0.001) and 0.8:1 in blood (P<0.05) in patients with sarcoidosis and high-intensity alveolitis. The ratio of helper to suppressor T cells was not higher in the lungs or blood of patients with sarcoidosis and low-intensity alveolitis; on the contrary, because of the higher proportions of suppressor cells, the ratio of helper to suppressor cells was lower in both lungs and blood. In studies of function, lung T cells from patients with sarcoidosis and high-intensity alveolitis released monocyte chemotactic factor (a lymphokine critical to granuloma formation) and polyclonally activated B cells to produce immunoglobulins. We conclude that one determinant of lung injury in sarcoidosis is the presence of large numbers of lung helper T cells, which are important in granuloma formation. (N Engl J Med. 1981; 305:429–34.)
Non–Cystic Fibrosis Bronchiectasis
Authors: Pamela J. McShane, Edward T. Naureckas, Gregory Tino, Mary E. Strek
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Section:ChooseTop of pageAbstract <<EpidemiologyPathogenesisEtiologyDiagnosisMicrobiologyManagementSurgeryConclusionsReferencesCITING ARTICLES